Central Illustration

Abstract

Alcohol is popular in Western culture, supported by a perception that modest intake is cardioprotective. However, excessive drinking has detrimental implications for cardiovascular disease. Atrial fibrillation (AF) following an alcohol binge or the “holiday heart syndrome” is well characterized. However, more modest levels of alcohol intake on a regular basis may also increase the risk of AF. The pathophysiological mechanisms responsible for the relationship between alcohol and AF may include direct toxicity and alcohol’s contribution to obesity, sleep-disordered breathing, and hypertension. We aim to provide a comprehensive review of the epidemiology and pathophysiology by which alcohol may be responsible for AF and determine whether alcohol abstinence is required for patients with AF.

What is the definition of a problem drinker? Someone who drinks more than his or her doctor. Although spoken in jest, a somewhat arbitrary distinction exists between the quantity of alcohol that is cardioprotective and that which is contributory to heart disease. Atrial fibrillation and/or flutter (AF) are the most common symptomatic arrhythmias worldwide, and the combination of an aging population and lifestyle factors has propelled AF to an “emerging epidemic” of cardiovascular disease. Increasingly, attention has shifted towards modifiable risk factors to prevent AF onset and progression.

The association between excessive drinking and various forms of cardiovascular disease is well established. In particular, significant alcohol consumption is associated with a higher risk of AF, hypertension, left ventricular hypertrophy (LVH), obstructive sleep apnea (OSA), and cardiomyopathy. However, smaller amounts of alcohol may reduce the incidence of coronary disease. Counterbalanced is an acceptance that even moderate levels of habitual consumption are associated with AF.

In this review, we examine published reports pertaining to alcohol and AF, including pathophysiology, the role of binge drinking, habitual consumption at all levels, links between alcohol and other AF risk factors, and prognostic implications.

Epidemiology

Alcohol is ubiquitous in Western countries, with 53% of Americans regularly consuming alcohol and 61 million (44% of drinkers) consuming ≥5 standard drinks on a single occasion (binge drinking) in the last month (1). “Holiday heart syndrome” (HHS) remains a common emergency department presentation, with AF precipitated by alcohol in 35% to 62% of cases (2,3). Three large meta-analyses have demonstrated that moderate habitual consumption, even after correcting for binge drinking, increases the incidence of AF in a dose-dependent manner (4–6), with men and women equally affected. Alcohol consumption has been defined as: light (<7 standard drinks/week); moderate (7 to 21 standard drinks/week); and heavy (>21 standard drinks/week), where 1 standard drink is approximately 12 g of alcohol.

The acute cardiac effects of alcohol in humans were first described in 14 patients who underwent electrophysiological studies before and after ∼5 standard drinks of whiskey. As in animal models, alcohol shortened the effective refractory period, and also slowed intra-atrial conduction (11). In a study of habitual moderate-heavy drinkers, ingestion of ∼6 standard drinks of whiskey prolonged the His-ventricular (H-V) interval and shortened sinus node recovery time, with an atrial or ventricular tachyarrhythmia inducible in 71% (12). Interatrial conduction, as determined by signal-averaged sinus P-wave duration, is significantly longer in patients with a history of AF following a binge compared with age-matched controls. However, following 1.5 g/kg ethanol, P-wave duration was prolonged in the control group with no history of AF (13), suggesting that alcohol directly slows interatrial conduction in all. Interatrial electromechanical delay has also been demonstrated acutely on tissue Doppler echocardiography (14).

In 48 patients with AF, atrial effective refractory periods were significantly shorter in drinkers compared with nondrinkers (15). Conduction slowing, in combination with shortening of atrial refractoriness, shortens wavelength and facilitates re-entry. To date, electrophysiological changes during the washout or hangover period have not been well characterized. Hypokalemia is also common in chronic heavy drinkers, and is primarily mediated by inappropriate kaliuresis from the coexistent hypomagnesemia present in 30% of heavy drinkers (16). Potassium loss may be exacerbated by vomiting during a binge, and predisposes to AF by increasing excitability, as cellular hyperpolarization lowers the resting membrane potential, which may increase sodium channel recruitment, leading to a faster upstroke.

Autonomic effects of alcohol

Alcohol has effects on autonomic modulation, which may contribute to AF. Mäki et al. (17) demonstrated a sympathetic response to 1.25 g/kg alcohol with a 29% increase in blood lymphocyte β-receptor density in patients with previous alcohol-induced AF. However, even lower alcohol doses stimulate the sympathetic nervous system, promoting adrenaline secretion from the adrenal medulla. Perman (18) found significant increases in urinary adrenaline excretion in 43 patients consuming 0.27 g/kg to 0.54 g/kg wine or whiskey, with differences seen even at alcohol concentrations <0.04%.

In patients without prior AF, there is a significant reduction in short-term heart rate variability (HRV) following acute alcohol ingestion (19). Süfke et al. (20) demonstrated a sustained increase in the ratio between low- and high-frequency components of HRV. This “hyperadrenergic state” persists at least 24 h after intoxication, and may explain why some patients present with AF the day after a binge.

Alcohol and Binge Drinking: “Holiday Heart Syndrome”

Ettinger et al. (33) first coined the term “holiday heart syndrome” (HHS) in 24 patients hospitalized with AF following a weekend binge. Although many of these were regular drinkers, subsequent studies showed that HHS also occurred in infrequent and nondrinkers after a binge (34). Interestingly, although many patients develop AF at the time of intoxication, others may present 12 to 36 h later (35). In fact, a “hangover” may be merely a manifestation of mild alcohol withdrawal, characterized by sympathetic hyperactivity, with a 17% heart rate increase observed in healthy nonalcoholics 12 h post-binge (36). Alcohol also has a diuretic effect, elevating antidiuretic hormone and aldosterone, potentially causing electrolyte disturbances that further contribute to a proarrhythmic state. Acetaldehyde, a potent cardiac toxin and alcohol metabolite, also has effects that may persist into the hangover period (37).

Although AF usually terminates within 24 h in HHS, 26% of patients have recurrences at 1 year with subsequent binges (38). Liang et al. (39) found that binge drinking (>5 standard drinks) in addition to habitual moderate consumption of ≤21 standard drinks/week was associated with a similar risk of AF as habitual heavy drinking.

Although HHS is often considered benign, heavy binge drinking has been linked with sudden cardiac death, particularly in patients with pre-existing structural heart disease. In 309 sudden cardiac death patients with 2.8 risk factors for coronary disease, the relative risk of dying within 2 h of drinking was 3.00 (95% confidence interval [CI]: 1.61 to 5.68) (40). In this vulnerable group, alcohol may precipitate ventricular tachycardia by QTc prolongation. Rossinen et al. (41) demonstrated QTc prolongation (13 ms to 25 ms; p <0.05) following 0.72 g/kg alcohol in patients with stable coronary disease, with similar findings unrelated to autonomic changes in healthy controls.

A meta-analysis of 29,457 participants in 23 studies demonstrated the complex physiological interplay of alcohol at different time points after consumption. Moderate consumption was associated with an immediately higher cardiovascular risk that was attenuated after 24 h, and became protective against ischemic stroke within 1 week. The investigators speculate that an increase in plasminogen activator inhibitor activity is responsible for events in the first 1 h to 3 h, with improvements in endothelial function, flow-mediated vasodilation, and fibrinolytic factors seen by 12 h to 24 h (42).

Habitual Alcohol Consumption as a Risk Factor for AF

Although heavy habitual alcohol consumption and binge drinking are closely associated with AF, the relationship between light-moderate habitual consumption and dose-dependent risk of AF has emerged in 3 large meta-analyses.

Larsson et al. (4) reported a 12-year follow-up of 859,420 patients together with a meta-analysis of 7 prospective studies, including 12,554 AF cases. After excluding binge drinkers and adjusting for other AF risk factors, all 7 studies reported a positive association between alcohol and AF. For each extra alcoholic drink per day, AF incidence increased 8%. The relative risks (RRs) were: 1.08 for 7 standard drinks/week (95% CI: 1.06 to 1.10); 1.17 for 14 standard drinks/week; 1.26 for 21 standard drinks/week; 1.36 for 28 standard drinks/week; and 1.47 for 35 standard drinks/week. Of those consuming >14 standard drinks/week, only wine (RR: 1.35; 95% CI: 1.08 to 1.68) and liquor (RR: 1.46; 95% CI: 1.18 to 1.81) were associated with AF, but not beer (RR: 1.03). This may be related to the higher alcohol concentration of wine and liquor, and differences in consumption behavior between drinkers of different beverages.

Kodama et al. (5) reported similar findings in an earlier meta-analysis of 14 retrospective and prospective studies, encompassing both case controls and cohort studies. The pooled estimate of RR for the highest category of alcohol consumption compared with the lowest category was 1.51 (95% CI: 1.31 to 1.74), with an 8% increase in AF risk for each 6 standard drinks/week consumed (5). Samokhvalov et al. (6) found a slightly higher threshold for AF risk, but also demonstrated a dose-response curve. The risk of AF was increased by 17% in women consuming >14 standard drinks/week and by 25% in men consuming >21 standard drinks/week (6).

Many of the individual studies were underpowered to demonstrate a relationship between alcohol and AF, particularly in the primary prevention population, where the incidence of AF was relatively low. Therefore, the conclusions regarding the relationship between low-moderate levels of alcohol intake and AF are largely drawn from the meta-analyses. There are important limitations when interpreting large population-based observational studies. Firstly, all studies (Table 1) determine the quantity of alcohol by self-reporting, rather than by objective blood or urine samples. This may have underestimated the AF risk due to under-reporting of alcohol consumption. Second, AF episodes may be asymptomatic, with the majority of studies largely relying on symptomatic episodes and presentation for electrocardiograms (ECGs), rather than dedicated monitoring. For instance, the Framingham (43) and Copenhagen City Heart (44) studies only performed routine ECGs every 2 to 4 and 5 to 10 years, respectively, with AF largely determined from hospital admissions, rather than routine monitoring or primary practice. Third, “AF events” often excluded atrial flutter. In studies (28,45,46) (Table 1) investigating patients with prior AF, the follow-up was generally shorter and the risk of AF recurrence consistently higher with light-moderate habitual consumption.

Major Studies Examining the Impact of Alcohol Consumption on AF and AFL∗

On the basis of the current review, we did not find a safe level of daily alcohol intake in patients with a history of AF; however, this recommendation is on the basis of observational and nonrandomized studies.

Heavy habitual consumption is a well-established risk factor for AF, and may be a more important risk factor than hypertension or obesity. In a cohort of 8,602 subjects, the HR of developing AF was 2.68 for heavy drinkers (≥40 standard drinks/week), compared with 1.72 for obesity and 1.02 for hypertension (47). In a longitudinal study of 26,163 earthquake survivors, drinking >25 standard drinks/week was the strongest predictor of AF, with a hazard ratio (HR) of 3.8, compared with HRs of 1.9 for obesity and 1.08 for hypertension (48).

Alcohol and Other AF Risk Factors: An Intermediary or a Confounding Variable?

Although there is little doubt that alcohol is independently associated with AF, its interaction with other AF risk factors, particularly in habitual drinkers, may be understated. In particular, hypertension, obesity, OSA, and cardiomyopathy may be caused or exacerbated by alcohol.

Alcohol may be responsible for 16% of hypertensive disease (49), with the incidence of hypertension increased by 40% if consuming >14 standard drinks/week. In a meta-analysis of 15 randomized trials, alcohol reduction significantly lowered systolic and diastolic blood pressures in a dose-dependent fashion (50). Hypertension may be present in up to two-thirds of AF patients (51), and AF is often preceded by LVH and atrial hypertrophy (52). In those with LVH, AF incidence is reduced by 40% if a systolic blood pressure <130 mm Hg is achieved (53).

Obesity is a powerful determinant of left atrial (LA) size and a well-recognized modifiable AF risk factor (54). Despite alcohol’s relatively high energy content, it has not been consistently shown to cause weight gain or metabolic syndrome in light-moderate drinkers (55). Moderate consumption (7 to 21 standard drinks/week) may even reduce new-onset diabetes by 30% (56). However, several observational studies indicate that drinking >21 standard drinks/week and binge drinking can increase body mass index, waist circumference, and waist-to-hip ratio (57). Recently published studies have focused on the benefits of structured weight reduction and exercise in reducing AF symptoms, beneficial cardiac remodeling, and sinus rhythm maintenance following PVI (54). The impact of the recommended intake of <3 standard drinks/week was not specifically addressed.

Although lighter alcohol intake may reduce the risk of heart failure, habitual heavy drinkers may experience the deleterious cardiotoxic effects of alcohol and develop an alcoholic cardiomyopathy. This may progress from unexplained LVH (64) to overt systolic heart failure, particularly if consuming >7 standard drinks/day for 5 years (65). Even if systolic function is normal, one-third of heavy drinkers have echocardiographic evidence of diastolic dysfunction, with deterioration of diastolic parameters correlating with degree of alcohol consumption (66). Elevated LA pressures associated with left ventricular diastolic and/or systolic dysfunction may predispose to AF by stretch-mediated mechanisms.

Alcohol and AF: Prognostic Implications

Those who continue to consume alcohol have higher rates of progression from paroxysmal to persistent AF, more AF recurrences following PVI, and potentially higher rates of adverse outcomes, such as thromboembolism.

In a cohort of paroxysmal AF patients, 70 of 418 (17%) progressed to persistent AF over 2.7 years. Moderate-heavy alcohol consumption (>14 standard drinks/week) was the strongest risk factor for progression (odds ratio [OR]: 3.0; 95% CI: 1.1 to 8.0) (45). Alcohol was also 1 of the strongest predictors of recurrent AF (RR: 2.3; 95% CI: 1.2 to 4.4) in patients with a first episode of “idiopathic” AF (46). In 122 consecutive patients undergoing PVI, 1-year arrhythmia-free survival was 81% in abstainers, 69% in light-moderate drinkers (1 to 14 standard drinks/week in men, 1 to 7 standard drinks/week in women), and 35% in “heavy” drinkers (28).

Nevertheless, the long-term cardiovascular benefits of light-moderate alcohol consumption are represented by a U-shaped curve derived from a meta-analysis (Central Illustration) (69). More than 100 nonrandomized studies have demonstrated that light-moderate intake (especially 7 standard drinks/week for women and 14 standard drinks/week for men) may decrease the risk of new-onset coronary artery disease, angina, myocardial infarction, and cardiovascular mortality (70) in nearly one-third of drinkers. The pooled RR for long-term cardiovascular mortality in drinkers was 0.75 (95% CI: 0.68 to 0.81) compared with nondrinkers. Proposed mechanisms include improved lipid profile (increased high-density lipoprotein, apolipoprotein A-I), and reduced platelet aggregation and inflammation (decreased interleukin-5, fibrinogen) (71). However, these studies predominantly included healthy adults, and should not be extended to those with a history of AF or structural heart disease.

Estimated long-term risk of developing atrial fibrillation (AF) and cardiovascular mortality in the general population with no prior history of AF on the basis of alcohol consumption in large meta-analyses. AF risk (blue line; average follow-up 12 years) as shown has been adapted with permission from Larsson et al. (4). Cardiovascular mortality (orange line; average follow-up 11 ± 6 years) as shown has been adapted with permission from Ronksley et al. (69).

Conclusions

Alcohol is an important risk factor for AF through direct effects on the atrial substrate, and by contributing to hypertension, obesity, and SDB. Habitual drinking at moderate levels, as well as binge drinking, predisposes to AF, with an increase in AF recurrence in those who continue to drink. Although a small amount of alcohol is considered cardioprotective, these benefits do not extend to AF.

Footnotes

Supported in part by the Victorian Government’s Operational Infrastructure Funding. Professor Kistler is supported by a practitioner fellowship from the National Health and Medical Research Council (NHMRC). Drs. Voskoboinik and Prabhu are supported by cofunded NHMRC/National Heart Foundation (NHF) post-graduate scholarships and Baker IDI Bright Sparks scholarships. Dr. Ling is supported by a post-doctoral fellowship from the NHF. Prof. Kalman has reported that he has no relationships relevant to the contents of this paper to disclose.

References

Center for Behavioral Health Statistics and Quality. Behavioral Health Trends in the United States: Results From the 2014 National Survey on Drug Use and Health (HHS Publication No. SMA 15-4927, NSDUH Series H-50). Available at: http://www.samhsa.gov/data. Accessed September 21, 2016.

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